The overall goal of the proposed research is to dissect the molecular mechanisms by which CD4+ T lymphocytes regulate the humoral immune response. CD4+ T cells provide contact dependent stimuli to B cells that are critical for the generation of specific antibody responses in a process termed T helper function. The surface structures on activated CD4+ T cells that mediate this function are not fully known. Central to this grant is the recent identification by our laboratory of a novel activation-induced 30 kD T cell surface protein (designated 5c8 Ag) that is expressed exclusively by activated CD4+ T cells in vitro and by germinal center T cells in vivo and is involved in mediating a contact dependent element of T helper function. Based on these findings, we propose to study the roles of 5c8 Ag in mediating discrete aspects of T helper functions. To characterize T help in further molecular detail, we propose to clone cDNAs encoding the 5c8 Ag and study the function of the 5c8 protein on novel cellular backgrounds and as soluble, recombinant forms of the protein. In addition, we propose to identify the B cell surface counter-receptor for 5c8 protein, clone cDNAs encoding this structure and map the precise peptide determinants that mediate the interaction of 5c8 protein and its counter-receptor. Together, these studies will shed new understanding on the processes by which T lymphocytes regulate the humoral immune response.